Effect of Sacubitril/Valsartan for HF Retained Across Range of eGFR Decline

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In an interview at ACC 2023, Safia Chatur, MD provided insight into the analysis of the PARADIGM-HF and PARAGON-HF trials, suggesting early eGFR changes should not deter continuation of sacubitril/valsartan.

The treatment effect of sacubitril/valsartan was retained across a wide range of estimated glomerular filtration rate (eGFR) decline in patients with heart failure (HF), according to a posthoc analysis of the PARADIGM-HF and PARAGON-HF trials.1

The findings indicate a moderate eGFR decline when transitioning from a renin-angiotensin system inhibitor (RASi) to an angiotensin receptor/neprilysin inhibitor (ARNI) was not consistently associated with the risk of subsequent clinical outcomes.

These data were presented at the American College of Cardiology (ACC) 2023 Annual Scientific Sessions in New Orleans, Louisiana.

Individuals with HF may experience transient changes in kidney function after the transition to sacubitril/valsartan, but it remains unknown whether the changes will influence the long-term benefit of the treatment. In the analysis, investigators looked to evaluate the association between the occurrence of moderate eGFR decline (>15%) after initial exposure to sacubitril/valsartan and subsequent cardiovascular outcomes and its treatment benefits.

Within sequential run-in phases, patients were titrated to enalapril 10mg twice daily and then 97/103 mg twice daily in PARADIGM-HF or valsartan 80mg twice daily and then sacubitril/valsartan 49/51 mg twice daily in PARAGON-HF. Among the randomized population, 11% of patients in PARADIGM-HF and 10% in PARAGON-HF were reported to have experienced eGFR decline during sacubitril/valsartan run-in.

However, eGFR partially recovered regardless of sacubitril/valsartan continuation or switch to RASI, post-randomization, according to investigators. In addition, the findings suggest the initial eGFR decline was not consistently associated with clinical outcomes in either trial. Data showed treatment benefits of sacubitril/valsartan on primary outcomes were similar irrespective of run-in eGFR decline in PARADIGM-HF (Pinteraction = .32) and PARAGON-HF (Pinteraction = .92).

Overall, the treatment effect of sacubitril/valsartan was reported to remain consistent across a range of eGFR declines. To gain more insight into the analysis, we sat down with presenting author Safia Chatur, MD, Brigham and Women’s Hospital at ACC 2023.

“What this analysis does that it helps a major barrier, or major perceived barrier, to the implementation of ARNI in this population,” Chatur told HCPLive. “Just as with angiotensin-converting enzyme (ACE) inhibitors, with angiotensin receptor blockers (ARBs), with mineralocorticoid receptor antagonists (MRAs), and sodium-glucose co-transporter 2 (SGLT2) inhibitors, what we see is that the early post-initiation eGFR changes really should not be a reason to limit optimization of drugs in the HF population."

Watch the rest of that interview here:


  1. Chatur S, Claggett BL, McCausland FR, Rouleau J, Zile MR, Packer M, Pfeffer MA, Lefkowitz M, McMurray JJ, Solomon SD, Vaduganathan M, Variation in Renal Function Following Transition to Sacubitril/Valsartan in Patients with Heart Failure, Journal of the American College of Cardiology (2023), doi: